Ascaridole, from terpinene

Singlet oxygen adds to cyclic 1,3-dienes to afford 1,4-endoperoxides 609). This type of reaction has first been applied successfully to the synthesis of ascaridole from a-terpinene 610) (6.4) and of the vesicatory compound cantharidine 6U) (6.5) some 25 years ago. 

Photooxygenation of a-terpinene 155 in the presence of eosin (equation 87) produces ascaridole 156, a constituent of the essential oil Chenopodium ambrosioides L 1. The ewrfo-peroxide 157 derived from cyclopentadiene is a crystalline solid, stable at —100 °C78 above this temperature it rearranges to a mixture of the bis-epoxide 158 and the epoxyaldehyde 159 (equation 88)79,80. 

Photolysis, in the presence of oxygen, of alkenes containing an ally lie hydrogen atom leads to the formation of hydroperoxides. The sensitized process is more efficient, and often yields photoproducts different in structure from those obtained by nonsensitized photooxidation. Cyclohexadiene and related dienes on photolysis in the presence of oxygen yield the transannular peroxides. Thus, on photosensitized oxidation, a-terpinene (410) is converted into ascaridole (411).435 The equivalent process is not, in general, observed in acyclic dienes. Certain polynuclear aromatic hydrocarbons, such as anthracene and naphthacene and including the heterocycles 5,10-diphenyl-1-... 

Under the same conditions ascaridole is formed from x-terpinene in high yield. 

A 2% solution of isoprene in dichloromethane and methanol with methylene blue or rose bengal as sensitizers gives, on irradiation under oxygen with a 500-W iodine lamp, a 50% yield of 4-methyl-l,2-dioxa-4-cyclohexene [52]. Cyclic dienes are converted into bicyclic endoperoxides (equation 132). The naturally occurring ascaridole is thus synthesized from a-terpinene (equation 133) [19, 1115]. 

Ascaridole, l-Methyl-4-i I-methylethyli-2 3-di-oxa bicycl o[2.2.2]oct-5-ene 1,4-peroxido -p-men thene -2 Ascarisin. C10H]4O2 mol wt 168.23. C 71.39%, H 9.59%, O 19.02%. An organic peroxide which constitutes 60-80% of oil of chenopodium. Synthesis from or-terpinene by treatment with oxygen, chlorophyll, and light Schenck, Ziegler, Naturwiss- 1964, 157. Purification Beckett et al, J. Pharm. Pharmacol 7, 55 (1955). 

The natural peroxide, ascaridole (10) could be biosynthesized by a O2 reaction from its diene precursor, a-terpinene (11). This reaction has been accomplished in vivo (Gollnick and Schenk, 1967). 

Oil of Chenopodium (wormseed oil). Essential oil obtained from Chenopodium ambrosioides var. anthel-minticum (goosefoot), previously used in humans and animals against worm parasites (eelworms and hookworms). O. C. is no longer used in human medicine on account of its side effects. O.C. contains mainly ascaridole (60-75%), ascaridole glycol, p-cymol (20-30%, see cymenes), a-terpinene, limo-nene. 

A [4 -F 2]-cycloaddition of singlet oxygen to a-terpinene in methanol yields ascaridole in the presence of catalytic amounts of Rose Bengal as photosensitizer. The reaction was carried out in one-channel chip microreador made from glass [73]. 

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